Abstract: A method for determining interaction of an analyte with a binding agent immobilized to a solid support surface by contacting the surface with a fluid sample containing the analyte, and detecting binding events at the solid support surface, wherein the sample is based on a complex medium containing at least one species other than analyte that may interact with the solid support surface, is disclosed. The method comprises contacting the solid support surface with sample medium free from analyte prior to contacting the surface with the analyte-containing sample.